The major goal of the proposed research is to elucidate the ultrastructural and functional mechanisms by which the thalamus controls cortical processing in the primate brain. In order to understand how early visual cortical networks function, it is important to recognize which circuits are dedicated to communicating the main message, which circuits regulate this message and how. Our specific thesis for this proposal is that all thalamic nuclei contain some cell groups that act as drivers and some that act as modulators for multiple cortical areas, thus mediating the generation of an array of diverse functions. The thalamus is not simply a passive relay to cortex. Instead, just as primary visual cortex (V1) depends on LGN, the secondary visual area (V2) and the middle temporal visual area (MT) depend on a combination of dedicated pathways through the thalamus (e.g., pulvinar) and direct feedforward connections from V1. Specifically, our hypothesis is that (1) both V1 and pulvinar act as drivers for specific functional cell groups in V2 and MT and (2) in addition to V2 and MT being modulators of V1, the pulvinar also acts as a modulator for V1. This arrangement allows new properties to emerge at both the thalamic and cortical levels through dynamic loops. Anatomical axonal signatures for drivers from LGN to V1 are known but it is not known if these signatures generalize to extrastriate cortical areas. We will examine for these light microscopic & ultrastructural signatures on pulvino- V2 and V1-V2 axons (AIM1). We will investigate whether the pulvinar provides a major functional drive for cell groups in V2 and MT (Aim 2) and a major modulatory input to V1 (Aim3). Finally, we will examine whether the pulvinar is much more than a mere relay and combines information from different pathways to synthesize complex functions within itself (Aim 4). In severe mental disorders including schizophrenia and Alzheimer's disease, the pulvinar exhibits lower metabolism, has smaller volume and fewer neurons. Understanding the normal functioning of pulvinar will shed light on the cause of some visual dysfunctions in these diseases. PUBLIC HEALTH RELEVANCE: Visual brain areas that are concerned with object recognition and complex motion are among the brain regions that have enlarged the most during the course of human evolution. One of these areas, the pulvinar, has recently been found to be severely affected in Alzheimer's disease and also to be involved in aspects of schizophrenia, yet very little is known about what this area does. The goal of this project is to understand the function of the pulvinar and its contribution to visual cortex.